The immunopathologic reaction of rabies virus infection is mainfested by early death in the presence of exogenous or endogenous antibody. Two hypotheses will tested: antibody of a given specificity, affinity and avidity kills rabies-infected animals directly; or antibody promotes killing of virus-infected mice indirectly by binding to target cells or to effector cells. Complement dependent cytotoxicity tests will be uded to characerize lytic antibody and the complement pathway will be explored. In cytotoxicity and blast transformation assays, the role of possible suppressor T cells inhibiting peritoneal T cell killer activity will be determined, followed by adoptive transfer experiments in mice. The effector cell type and antibody class responsible for antibody dependent cellular cytotoxicity will be explored to define in vivo the rabies immunopathologic reaction. Finally, the role of defective-interfering particles in etiology of early death and in its prevention will be tested.